Rubio's broad losses were not a surprise in the conservative South.
But his rationale for staying in the race was undermined when rival Ted Cruz picked up his home state of Texas and neighboring Oklahoma, giving Cruz a total of three states to Rubio's one.
That's given Cruz a strong case to argue that he, rather than Rubio, is best positioned to take on front-runner Donald Trump.
Rubio will push for a victory on March 15 in Florida, his home state. But his prospects there have dimmed as polls show Trump widening his lead among Republican voters.
"We're going to be in this race as long as it takes," Rubio said on television late Tuesday, as votes were still being counted in Minnesota.
Team Rubio warned of the "long war on Trump" ahead in a fundraising note as results rolled in Tuesday.
"This is going to be a long campaign, and we are NOT going to hand our party over to a dangerous con artist," the message said.
Rubio argues that he can still amass delegates and that he will do better on politically friendlier terrain in the states ahead than Cruz, who had staked his strategy on sweeping the conservative and religious South.
“Two weeks from tonight, right here in Florida, we are going to send a message loud and clear,” Rubio said in Miami. “We are going to send a message that the party of Lincoln and Reagan, and the presidency of the United States, will never be held by a con artist.”
But the optics of a campaign that has only won one state could be damaging.
A super PAC announced late Tuesday it was "intensifying" efforts to stop Trump, which could benefit Rubio. The Florida senator is still preferred by many in Washington over Cruz, who has alienated much of the GOP establishment.
The super PAC, funded in part by the wealthy Ricketts family and staffed by a former top aide to Jeb Bush, plans daily attacks on Trump's record and business dealings in an effort to stop the businessman from collecting enough delegates to lock up the nomination.
Trump, speaking at his resort hotel in Palm Beach, Fla., dismissed Rubio's "bad night."
"He hasn't won anything," Trump said.
And Cruz suggested at his election event in Texas that those who have yet to win a state should "prayerfully consider coming together, unifying."
In other words, he called on Rubio and two other GOP candidates -- Ohio Gov. John Kasich and Ben Carson -- to drop out so he could go head-to-head against Trump.
After months of delivering an optimistic message, Rubio shifted tactics and began to take Trump on directly last week with his own slashing insults and jibes.
Rubio spent the last few days trash-talking, criticizing the billionaire's "spray tan," short fingers and business ethics. It's unclear whether the attempt to match Trump's coarse campaign style helped Rubio, however.
Times staff writer Seema Mehta contributed to this report.
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